Cell nuclei catalyze the formation of free radical forms of anticancer drugs such as daunorubicin, adriamycin, mitomycin C, streptonigrin, and actinomycin D. Purified bovine milk xanthine oxidase also catalyzes free radical formation with the anthracycline antibiotics. Xanthine oxidase also functions as a reductive glycosidase with anthracyclines and catalyzed their cleavage to deoxyaglycone products. A free radical intermediate is proposed for this cleavage mechanism. At least two different groups of daunorubicin reductases occur in human, rabbit, rat, and mouse tissues with pH optima at 6.0 and 8.5. The pH 6.0 enzyme appears to be the major aldo-keto reductase component of most normal tissues.